Dental innervation is still not fully understood concerning its variety of nerve fibers, their interactions with pulp and dentin in normal teeth, and the mechanisms that cause hypersensitive dentin, postoperative pain, and difficult anesthesia for inflamed teeth. There is important plasticity in expression of sodium channels in injured cutaneous sensory neurons, driven by neurotrophic factors, but it is not known whether similar events underlie persistent neuroplasticity and pain after tooth injury. Teeth are an excellent model tissue for studying neuroinflammatory interactions in the periphery and their effects on trigeminal nerves, the ganglion and the central nervous. Tooth injury also affects non-dental neurons in the ganglion, in the brain stem and sometimes in contralateral trigeminal neurons by mechanisms that in part depend on paracrine signalling by nerve growth factor. The Aims of this work are: (1) to determine the effects of specific types of tooth injury on sodium channel expression in dental neurons, neighboring uninjured trigeminal neurons and central neurons in relation to pain behavior, pulpal pathology and anti-inflammatory treatment, (2) to determine whether trigeminal sodium channel expression, pulpal reactions and behavior are affected in mutant mice that have altered neurotrophin mechanisms, and (3) to define the complexities of cells in the pulp, especially the odontoblast layer, in relation to expression of neurotrophins and calcium channels, in order to better understand the pulpal-nerve interactions in normal and injured teeth. We will use dental injury models in rats and mutant mice for analysis by behavioral testing, immunocytochemistry and in situ hybridization. There will be specific labeling of injured dental neurons by retrograde transport of fluorogold for comparison with uninjured labeled neurons. Our newly developed behavioral assays allow the characterization of pain periods in relation to pulpal and neural cytochemistry during anti-inflammatory treatment or in mutant mice. Our goal is to understand neuroinflammatory interactions in inflamed teeth in order to develop better treatments for dental pain.